On March 17, 2015 Biogen reported interim results of its recent clinical trial using an antibody to treat Alzheimer’s disease. These results were extremely encouraging as they demonstrated both significant reductions in amyloid and improvements in cognition in patients with Alzheimer’s disease. This success is certain to stimulate new enthusiasm for investing in clinical trials in the disorder.

The Biogen study was a Phase 1 trial, designed primarily to determine safety and tolerability of the treatment. The study renews support for the amyloid hypothesis of Alzheimer’s disease, a theory that has been severely challenged after clinical setbacks from recent Phase 3 trials using other amyloid antibodies.

166 patients were enrolled in the study and results were presented after 54 weeks of treatment. Four doses of drug were delivered: 1mg/kg (n = 31 patients); 3mg/kg (n = 33 patients), and 10 mg/kg (n = 32 patients). An additional dose of 6mg/kg was administered (n = 30 patients), although subjects receiving this dose have not yet reached the 54-week time point. Results were compared to placebo-controlled patients (n = 40 patients).

Based on the positive results, Biogen is moving straight to a Phase 3 study, planning to begin enrolling patients by the end of 2015.

The results of this study are very encouraging; however, it is still important to sound a note of caution: other studies have shown early promise, but this promise has not been fulfilled in Phase 3 trials in which sufficiently large numbers of patients were enrolled to test whether the drug was efficacious. Indeed, a quote in Forbes magazine by a key opinion leader in the Alzheimer’s field echoed this concern: “I personally don’t put any stock in the clinical outcomes because the sample size is so small,” says Lon S. Schneider, a professor of psychiatry and behavioral sciences at the University of Southern California’s Keck School of Medicine. Dr. Schneider pointed out that just adding or subtracting a few patients from the placebo group could meaningfully change the result. It should also be noted that the 40 patients in the placebo group were not treated fully in parallel with groups receiving the antibody (for instance, the 6 mg/kg group was started later than the placebo group), which could impact test results.

This type of antibody treatment has previously been shown to cause the induction of amyloid-related imaging abnormalities (ARIA) in Alzheimer’s disease, a side effect that can result from edema or micro-hemorrhage. Both ARIA and headache were noted as dose-dependent side effects of treatment in the Biogen trial; however, these adverse effects may be managed by using lower doses of the drug.

Despite these safety concerns I believe that Biogen’s latest study gives cause for optimism: it provides renewed support for the modulation of amyloid as a disease-modifying approach and, because Biogen is using larger number of subjects earlier in its trials, offers a path for shortening the lengthy drug development process.